Medical Treatment of Colitis in Patients With Hermansky-Pudlak Syndrome
- Conditions
- Hermanski-Pudlak SyndromeColitisCytokinesLymphocytesDrug Evaluation
- Interventions
- Registration Number
- NCT00514982
- Brief Summary
This study will determine if medical treatment of colitis (inflammation of the colon resulting in loose bowel movements, rectal bleeding, and belly pain) that is used for other colitis conditions, such as Crohn's disease and ulcerative colitis, is safe and effective for treating colitis in patients with Hermansky-Pudlak syndrome (HPS). HPS is a hereditary disorder that causes albinism, visual impairment, and abnormal bleeding. Some patients also develop colitis, pulmonary fibrosis, and kidney disease.
Patients with HPS and colitis who are 18 years of age or older may be eligible for this study. Participants receive treatment for their colitis symptoms with one or more of several study drugs, which include mesalamine (5-ASA), corticosteroids, infliximab and 6-mercaptopurine, adalimumab and tacrolimus. The drugs are added to the treatment plan one at a time to find the combination that works best for the individual patient. Patients who respond to one or more of the medications may continue treatment with that same combination for up to 6 months.
Regular clinic visits are scheduled for blood tests, symptoms ratings questionnaires and periodic physical examinations and colonoscopies to measure the response to treatment and evaluate any side effects.
- Detailed Description
The primary purpose of this study is to detect patterns of immune abnormalities in the colitis associated with Hermansky-Pudlak Syndrome (HPS). Additionally we aim to document the clinical response to and tolerance of conventional inflammatory bowel disease (IBD) therapy for HPS patients with active colitis associated with Hermansky-Pudlak Syndrome (HPS). HPS is a rare autosomal recessive disorder causing dysfunctional lysosome-related organelle formation and trafficking resulting in oculocutaneous albinism and a bleeding diathesis secondary to platelet dysfunction. Associated conditions include pulmonary fibrosis, IBD, and systemic ceroid deposition. The associated IBD has been reported to occur at a higher frequency in the HPS-1 and HPS-4 subtypes compared to the prevalence of IBD in non-HPS populations. HPS IBD has clinical features of both ulcerative colitis (UC) and Crohn's disease, but histologically resembles Crohn's disease in that granulomas are commonly seen in the mucosa of the intestine. The pathogenesis of HPS IBD is not fully understood and little data beyond descriptions of the clinical and histologic manifestations have been published. Furthermore reports on treatment of the colitis in HPS patients are largely anecdotal, and our own experience suggests that many patients may be under-treated.
HPS patients with active colitis will be enrolled into this prospective treatment study. Endpoints for the immunopathogenesis studies will include baseline measurements of and changes in immune cell populations, cytokine, and chemokine expression. In the blood and gut mucosa. Endpoints for the study of response to treatment will include changes in clinical, endoscopic, and histologic scores as well as the rate and severity of adverse events. Descriptive summary statistical analysis (n, mean, median, standard deviation, minimum and maximum range) and simple correlations of clinical response variables with immune parameters will be done.
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description 1/Drug#2 Corticosteroids Add oral corticosteroids (prednisone) to mesalamine. The standard induction dose will be 40 mg/day. After 1 week of therapy, if the total SCCAI score has decreased by greater than or equal to 2 points the patient will continue on another week of therapy. If the SCCAI has not decreased by greater than or equal to 2 points (indicative of a reduction in symptoms) at one week, then the dose will be increased to 60 mg/day. Patients on either dosage will have another SCCAI assessment done a week later (2 weeks after beginning corticosteroids), and if they are found to be in remission (SCCAI less than or equal to 2), a steroid-tapering schedule will be initiated. 1/Drug#6 Tacrolimus Patients who have a SCCAI greater than 2 after 2 doses of adalimumab will continue 6-MP, discontinue adalimumab, and start therapy with tacrolimus 0.01 mg/kg PO BID approximately 2 weeks after the second dose of adalimumab. 1/Drug #1 Mesalamine Oral mesalamine will be used as initial therapy in patients who are not taking any medication or have not received any prior treatment for their IBD. Dosing will begin at 2.4 g PO QD and will be increased to 4.8 g QD within 2 weeks. Topical mesalamine (enema 4 g PR HS/BID or suppository 1 g PR HS/BID) may be added for patients with inflammation that is limited to the rectum (proctitis) or who have prominent complaints of urgency, incomplete evacuation or rectal bleeding. 1/Drug#3 6-Mercaptopurine Infliximab and 6-MP will be added to patients with a SCCAI greater than 2 at week 8. The first infusion of infliximab (5 mg/kg) will be given during that week. In addition, 6-MP will be initiated at doses of 1.0-1.5 mg/kg PO QD to reduce the incidence of infliximab antibody formation and facilitate steroid tapering (the target dose of 6-MP will be decreased accordingly if patients are found to have low TMPT levels/activity by genotypic or phenotypic testing). Also, steroids will also be rapidly tapered off at this time. 1/Drug#4 Infliximab Infliximab and 6-MP will be added to patients with a SCCAI greater than 2 at week 8. The first infusion of infliximab (5 mg/kg) will be given during that week. In addition, 6-MP will be initiated at doses of 1.0-1.5 mg/kg PO QD to reduce the incidence of infliximab antibody formation and facilitate steroid tapering (the target dose of 6-MP will be decreased accordingly if patients are found to have low TMPT levels/activity by genotypic or phenotypic testing). Also, steroids will also be rapidly tapered off at this time. 1/Drug#5 Adalimumab Subjects with a SCCAI greater than 2 after 3 doses of infliximab will continue 6-MP, discontinue infliximab infusions and start adalimumab injections approximately 2 weeks after the 3rd dose of infliximab. Induction dosing will consist of a 160 Micro/g subcutaneous injection, followed by 80 Micro/g 2 weeks after.
- Primary Outcome Measures
Name Time Method To detect patterns of immune abnormalities in the colitis associated with Hermansky-Pudlak Syndrome (HPS). 60 weeks
- Secondary Outcome Measures
Name Time Method Document the clinical response to and tolerance of conventional inflammatory bowel disease (IBD) therapy for HPS patients with active colitis associated with Hermansky-Pudlak Syndrome (HPS). 60 weeks
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States